Reviewers skeptical of Sarepta therapy, documents show
Reviewers at the Food and Drug Administration concluded that Cambridge biotech Sarepta Therapeutics did not show that its gene therapy for Duchenne muscular dystrophy will likely benefit patients and left key safety concerns, according to briefing documents released Wednesday.
The FDA documents, released ahead of an advisory committee hearing Friday, found that Sarepta’s clinical studies “conducted to date do not provide unambiguous evidence” that the therapy, known as SRP-9001, is “likely beneficial for ambulatory patients” with Duchenne.
Additionally, the reviewers feared that administering a potentially “ineffective gene therapy” could both expose patients to safety risks — such as liver damage — associated with viral gene therapy, while also making those patients ineligible for other gene therapies in the future.
Details from the 55-page review are consistent with STAT’s reporting last month that certain officials inside the agency were planning to recommend rejecting Sarepta’s application, before the agency’s head of biologics, Peter Marks, intervened to convene the hearing.
The agency is now bringing together 13 independent experts to discuss the company’s application. The FDA has asked the experts to vote at the conclusion of Friday’s hearing on whether to recommend the approval of Sarepta’s gene therapy. The vote is nonbinding but could sway the agency’s decision, which is expected at the end of May.
It is one of the most pivotal moments in recent memory for Duchenne patients and their families, many of whom have seen this therapy as the best hope for slowing the fatal musclewasting disease.
Sarepta’s gene therapy is designed to deliver a shortened version of dystrophin, the gene broken in Duchenne, because the full-length version of the gene is too long to fit in the standard viruses used for gene therapy. Sarepta applied for accelerated approval — in which drugs are provisionally approved given early evidence — based on data showing the therapy delivers high levels of microdystrophin to patients’ cells.
The proceedings will also be closely watched by others in the rare disease and gene therapy world, as it is the first time a company has asked the FDA to give a gene therapy accelerated approval.
The documents show, however, that the agency told Sarepta as far back as 2018 that microdystrophin is unlikely to be a suitable endpoint for accelerated approval, as it has substantive differences from both the fulllength gene and shortened but functional forms of the gene found in rare, relatively healthy individuals.
And the company’s animal data and clinical trials, the agency said, did not prove that increasing microdystrophin correlates with increased muscle function.